Cited by 598Gut microbiota and healthGenetic Associations and EpidemiologyNutrition, Genetics, and Disease

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Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project

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Lopera-Maya, Esteban A., Kurilshikov, Alexander, van der Graaf, Adriaan, Hu, Shixian, Andreu-Sánchez, Sergio, Chen, Lianmin, Vila, Arnau Vich, Gacesa, Ranko, Sinha, Trishla, Collij, Valerie, Klaassen, Marjiolein A. Y., Bolte, Laura A., Gois, Milla F. Brandao, Neerincx, Pieter B. T., Swertz, Morris A., LifeLines Cohort Study, Aguirre-Gamboa, Raul, Deelen, Patrick, Franke, Lude, Kuivenhoven, Jan A., Lopera-Maya, Esteban A., Nolte, Ilja M., Sanna, Serena, Snieder, Harold, Swertz, Morris A., Vonk, Judith M., Wijmenga, Cisca, Harmsen, Hermie J. M., Wijmenga, Cisca, Fu, Jingyuan, Weersma, Rinse K., Zhernakova, Alexandra, Sanna, Serena·2022·Nature Genetics

DOI 10.1038/s41588-021-00992-y

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Abstract

Host genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function in 7,738 participants of the Dutch Microbiome Project. Two robust, study-wide significant (P < 1.89 × 10−10) signals near the LCT and ABO genes were found to be associated with multiple microbial taxa and pathways and were replicated in two independent cohorts. The LCT locus associations seemed modulated by lactose intake, whereas those at ABO could be explained by participant secretor status determined by their FUT2 genotype. Twenty-two other loci showed suggestive evidence (P < 5 × 10−8) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci we identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome. A genome-wide association study of 207 taxa and 205 pathways representing gut microbial composition and function from 7,738 individuals of the Dutch Microbiome Project identifies genetic associations at the LCT and ABO loci.

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Authors: Lopera-Maya, E. A., Kurilshikov, A., van der Graaf, A., Hu, S., Andreu-Sánchez, S., Chen, L., Vila, A. V., Gacesa, R., Sinha, T., Collij, V., Klaassen, M. A. Y., Bolte, L. A., Gois, M. F. B., Neerincx, P. B. T., Swertz, M. A., Study, L. C., Aguirre-Gamboa, R., Deelen, P., Franke, L., Kuivenhoven, J. A., Lopera-Maya, E. A., Nolte, I. M., Sanna, S., Snieder, H., Swertz, M. A., Vonk, J. M., Wijmenga, C., Harmsen, H. J. M., Wijmenga, C., Fu, J., Weersma, R. K., Zhernakova, A., & Sanna, S.
Affiliations: University Medical Center Groningen (NL)
Corresponding author: Zhernakova, Alexandra
ORCID: Kurilshikov, Alexander
van der Graaf, Adriaan
Hu, Shixian
Andreu-Sánchez, Sergio
Chen, Lianmin
Vila, Arnau Vich
Gacesa, Ranko
Sinha, Trishla
Collij, Valerie
Bolte, Laura A.
Gois, Milla F. Brandao
Neerincx, Pieter B. T.
Deelen, Patrick
Franke, Lude
Kuivenhoven, Jan A.
Nolte, Ilja M.
Snieder, Harold
Vonk, Judith M.
Harmsen, Hermie J. M.
Fu, Jingyuan
Weersma, Rinse K.
Zhernakova, Alexandra
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 2022-02
Volume: 54
Issue: 2
Pages: 143-151
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/s41588-021-00992-y
OpenAlex: W4225566784
Cited by: 553
References: 84
Citations by year: 2026: 107 · 2025: 153 · 2024: 156 · 2023: 105 · 2022: 28
FWCI: 39.64
Type: journal article
Language: en
Update notices: correction (2022-07-25)
Open access: hybrid
doi.org
Licence: other-oa
www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Genetics (publishedVersion, other-oa)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Funders: Departamento Administrativo de Ciencia, Tecnología e Innovación (COLCIENCIAS)
Seerave Foundation (715772, 2018-27, 016.178.056)
Stichting De Cock-Hadders (20:20-13)
Rijksuniversiteit Groningen (2018-27, 715772)
Ministerie van Volksgezondheid, Welzijn en Sport (024.003.001)
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO Gravitation grant Exposome-NL 024.004.017, NWO SPI 92–266, 024.003.001, Exposome‐NL 024.004.017, 024.003, 016.178.056, 016.Vidi.178.056, 024.004.017, SPI 92-266)
China Scholarship Council (024.004.017, CSC 201708320268)
Universitair Medisch Centrum Groningen
Interreg (202085)
H2020 European Research Council (101001678, 715772)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
Keywords: host genetics, gut microbiota, microbial community composition, microbial function, LCT gene, ABO gene, lactose intake, genetic association
MeSH terms: ABO Blood-Group System, Gastrointestinal Microbiome, Host Microbial Interactions, Galactoside 2-alpha-L-fucosyltransferase, Bifidobacterium, Diet, Fucosyltransferases, Humans, Netherlands, Triglycerides, Genetic Variation, Genome, Human, Sodium Chloride, Dietary, Bacterial Physiological Phenomena, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Gastrointestinal Tract, Lactase, Metabolic Networks and Pathways, Metagenome, Genome-Wide Association Study

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